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Involvement of Homologous Recombination in Response to Different Qualities of DNA Damage
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The present studies aimed at elucidate the role of homologous recombination (HR) for the repair of different qualities of DNA damages and/or changes in chromatin structure induced by a variety of radiation qualities.

Radiation qualities used to expose cells in culture ranged from non-ionizing radiation with extremely low frequency (ELF), of energies too low to disrupt chemical or molecular bonds, to radiation qualities with energies able to induce ionizations and break chemical bonds. The ionizing radiation (IR) used was both of low- or high-linear energy transfer (LET) producing a range of ionization densities. The higher the ionization density, the worse the cellular outcome in terms of survival, this can also be described as higher relative biological effectiveness (RBE).

Homologous recombination that is involved in the repair of double-strand breaks operates mainly in the S and G2/M-phases of the cell cycle when a sister chromatid with the required homology sequence is available as template. HR is also involved in reinitiating stalled or collapsed replication forks, which may be the main task for this pathway.

The data obtained with non-ionizing radiation suggest that ELF exposure may either stimulate or inhibit cell growth depending on the state of the cells in terms of chromatin conformation. Although ELF magnetic fields are not directly capable of inducing DNA breaks, a weak but significant increase in DNA fragmentation was observed. However, no induction of HR was indicated. Neither did ELF increase chromatin loop relaxation.

A novel finding presented here is that HR seems to process DSBs produced by high-LET relatively more frequently compared to DSBs produced by low-LET. These results in combination with data suggesting that HR (as well as the fast NHEJ and BER) predominantly operates in open chromatin would indicate that a substantial fraction of DSBs induced by high-LET may also originate from the indirect effect.

Place, publisher, year, edition, pages
Stockholm: Institutionen för genetik, mikrobiologi och toxikologi , 2005. , 35 p.
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:su:diva-451ISBN: 91-7155-061-5 (print)OAI: oai:DiVA.org:su-451DiVA: diva2:194055
Public defence
2005-04-29, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 8 C, Stockholm, 13:00
Opponent
Supervisors
Available from: 2005-04-07 Created: 2005-04-07Bibliographically approved
List of papers
1. ELF magnetic field affects proliferation of SPD8/V79 Chinese hamster cells but does not interact with intrachromosomal recombination
Open this publication in new window or tab >>ELF magnetic field affects proliferation of SPD8/V79 Chinese hamster cells but does not interact with intrachromosomal recombination
2001 In: Mutation Research, ISSN 1383-5718, Vol. 493, no 1-2, 55-66 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-23703 (URN)
Note
Part of urn:nbn:se:su:diva-451Available from: 2005-04-07 Created: 2005-04-07Bibliographically approved
2. Induction of homologous recombination in the hprt gene of V79 Chinese hamster cells in response to low- and high-LET irradiation
Open this publication in new window or tab >>Induction of homologous recombination in the hprt gene of V79 Chinese hamster cells in response to low- and high-LET irradiation
2004 In: Cytogenet Genome Res, Vol. 104, no 1-4, 227-231 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-23704 (URN)
Note
Part of urn:nbn:se:su:diva-451Available from: 2005-04-07 Created: 2005-04-07Bibliographically approved
3. Chromatin structure a determinant of gamma-radiation induced DNA-double strand breaks, repair pathways and toxicity, as indicated from differential protection by the radical scavenger DMSO
Open this publication in new window or tab >>Chromatin structure a determinant of gamma-radiation induced DNA-double strand breaks, repair pathways and toxicity, as indicated from differential protection by the radical scavenger DMSO
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Manuscript (Other academic)
Identifiers
urn:nbn:se:su:diva-23705 (URN)
Note
Part of urn:nbn:se:su:diva-451Available from: 2005-04-07 Created: 2005-04-07 Last updated: 2010-01-13Bibliographically approved

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